Galanin mediates tumor-induced immunosuppression in head and neck squamous cell carcinoma.
Galanin mediates tumor-induced immunosuppression in head and neck squamous cell carcinoma.
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DOI：
10.1007/s13402-021-00631-y
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发表时间：
2022-04
影响因子：
6.6
通讯作者：
Rossa Jr, Carlos
中科院分区：
文献类型：
--
作者：
de Medeiros, Marcell Costa;Liu, Min;Banerjee, Rajat;Bellile, Emily;D'Silva, Nisha J.;Rossa Jr, Carlos
甘丙肽受体 2 (GALR2) 在头颈鳞状细胞癌 (HNSCC) 的进展中发挥重要作用。由于实际上没有关于肿瘤微环境中其配体介导的免疫调节的信息，我们评估了甘丙肽对外周血单核细胞（PBMC）的影响。在验证 PBMC 中的 GALR2 表达及其活性后，我们评估了甘丙肽和来自甘丙肽沉默或抗体耗尽的 HNSCC 细胞系的条件培养基对免疫细胞的增殖、凋亡、细胞因子表达和激活/分化的影响。我们发现单独的甘丙肽和作为 HNSCC 分泌组的一个组成部分可降低 HNSCC 细胞增殖和促炎细胞因子（IFNγ、IL-12、IL-17A、IL-1α、IL-6 和 TNF-α）的表达，同时增加细胞凋亡和促肿瘤细胞因子/生长因子（IL-10、IL-4、PDGF 和 GM-CSF）的表达。发现 CD4+ T 细胞（Th1 和 Th17）中的 T 细胞激活（使用 CD69 作为激活标记）和抗肿瘤表型受到抑制。在体内，发现甘丙肽刺激的 PBMC 存在时肿瘤生长会增加。癌症基因组图谱 (TCGA) 的数据显示，甘丙肽的高表达与 HNSCC 患者的总生存期降低相关。我们的数据表明，HNSCC 细胞分泌的甘丙肽具有免疫抑制和促肿瘤作用。在线版本包含可在 10.1007/s13402-021-00631-y 获取的补充材料。
Galanin receptor 2 (GALR2) plays a significant role in the progression of head and neck squamous cell carcinomas (HNSCC). Since there is virtually no information on immunomodulation mediated by its ligand in the tumor microenvironment, we assessed the effects of galanin on peripheral blood mononuclear cells (PBMCs). After verification of GALR2 expression and it activity in PBMCs we evaluated the effect of galanin and conditioned media from HNSCC cell lines silenced for galanin or antibody-depleted, on proliferation, apoptosis, cytokine expression and activation/differentiation of immune cells. We found that galanin alone and as a component of the HNSCC secretome decreased HNSCC cell proliferation and expression of pro-inflammatory cytokines (IFNγ, IL-12, IL-17A, IL-1α, IL-6 and TNF-α), whilst increasing apoptosis and expression of pro-tumoral cytokines/growth factors (IL-10, IL-4, PDGF and GM-CSF). T cell activation (using CD69 as activation marker) and anti-tumoral phenotypes in CD4+ T cells (Th1 and Th17) were found to be suppressed. In vivo, tumor growth was found to be increased in the presence of galanin-stimulated PBMCs. Data from The Cancer Genome Atlas (TCGA) revealed that high expression of galanin was associated with a reduced overall survival of patients with HNSCC. Our data indicate that galanin secreted by HNSCC cells exhibits immune-suppressive and pro-tumoral effects. The online version contains supplementary material available at 10.1007/s13402-021-00631-y.
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影响因子：
3.6
作者：
Jimenez-Andrade, Juan Miguel;Lundstrom, Linda;Carlton, Susan M.
通讯作者：
Carlton, Susan M.
影响因子：
8.8
作者：
Balermpas, P;Michel, Y;Wagenblast, J;Seitz, O;Weiss, C;Rodel, F;Rodel, C;Fokas, E
通讯作者：
Fokas, E
DOI：
10.1002/hed.25930
发表时间：
2019-10-01
影响因子：
2.9
作者：
Kao, Hsiang-Fong;Lou, Pei-Jen
通讯作者：
Lou, Pei-Jen
影响因子：
5.7
作者：
Banerjee R;Van Tubergen EA;Scanlon CS;Vander Broek R;Lints JP;Liu M;Russo N;Inglehart RC;Wang Y;Polverini PJ;Kirkwood KL;D'Silva NJ
通讯作者：
D'Silva NJ
影响因子：
6.4
作者：
Balermpas, Panagiotis;Roedel, Franz;Fokas, Emmanouil
通讯作者：
Fokas, Emmanouil